Dicarbonyl Electrophiles Mediate Inflammation-Induced Gastrointestinal Carcinogenesis

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Differing Effects of Interleukin-10 on Cutaneous and Pulmonary Francisella tularensis Live Vaccine Strain Infection

We investigated the role of interleukin-10 (IL-10) in cutaneous and pulmonary infection with Francisella tularensis. We found that after intradermal challenge of mice with the live vaccine strain (LVS) of F. tularensis, splenic IL-10 levels increased rapidly and reached a peak 5 days after infection. However, IL-10 expression after infection was detrimental, since IL-10^−/− mice showed increased bacterial clearance and were resistant to an infectious dose (>10⁶ CFU/mouse) that was uniformly lethal for IL-10^+/+ mice. Furthermore, IL-10^+/+ mice treated with neutralizing anti-IL-10R monoclonal antibody were able to survive lethal cutaneous LVS challenge. The presence of IL-10 appeared to restrain the expression of IL-17, since high levels of splenic IL-17 were observed after intradermal LVS infection only in IL-10^−/− mice. Furthermore, treatment with neutralizing anti-IL-17R antibody ablated the enhanced survival observed in IL-10^−/− mice. However, neutralization of IL-10 activity in IL-17R^−/− mice failed to provide protection. Thus, IL-10 suppresses a protective IL-17 response that is necessary for resistance to cutaneous LVS infection. Surprisingly, however, IL-10^−/− mice were significantly more susceptible to pulmonary infection with LVS. Finally, although IL-10 is a critical and novel regulator of immunity to F. tularensis LVS infection, its effects were masked during infection with the highly virulent SchuS4 strain. Taken together, these findings suggest that differentially regulating expression of the IL-10 pathway in various tissues could ultimately have prophylactic and therapeutic benefits for protection against tularemia.     

Linezolid resistance in a clinical isolate of Staphylococcus aureus

The new oxazolidinone antimicrobial, linezolid, has been approved for the treatment of infections caused by various gram-positive bacteria, including meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Although instances of linezolid resistance in VRE have been reported, resistance has not been encountered among clinical isolates of S aureus. We have characterised an MRSA isolate resistant to linezolid that was recovered from a patient treated with this agent for dialysis-associated peritonitis.     

Prevention of musculoskeletal conditions in the developing world

Musculoskeletal conditions are an increasingly common problem across the globe due to increased longevity and increased exposure to risk factors such as obesity and lack of physical activity. The increase is predicted to be greatest in developing countries, and there is thus an urgent need for the implementation of strategies and policies that will prevent and control these conditions. The ideal is modification of the risk factors in the whole community, and this will have wide-ranging health benefits as these risk factors are common to other major conditions. Changing people's behaviour is a challenge; targeting those at highest risk is potentially more effective, providing that there are both affordable ways of identifying those at risk and affordable interventions. Early intervention in those with a condition such as rheumatoid arthritis is probably the most cost-effective approach, but requires diagnostic capacity - in clinical skills and/or technology - as well as access to care. There is now much evidence for what can be achieved, but the challenge is how to implement these different strategies in developing countries where there are competing priorities for limited resources. The key strategy is to raise awareness among the public, health professionals, and policy makers of the importance of musculoskeletal health, of what can be achieved by prevention and treatment, and to ensure that policies reflect this. It is also necessary to educate the public to know when to seek care, and health-care workers to recognize the early signs of musculoskeletal conditions.     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.